There are numerous reasons for determining the level of glucose present in body fluid of a subject. In the case of a person suffering from diabetes, it is often necessary to determine the glucose level in blood daily, or even more frequently. Non-invasive approaches to determination of blood glucose levels have been suggested in the patent literature. For example, U.S. Pat. No. 5,036,861 (issued to Sembrowich et al. on Aug. 6, 1991) describes a wrist-mountable device having an electrode which measures glucose present in sweat at the skin surface. U.S. Pat. No. 5,222,496 (issued to Clarke et al. on Jun. 29, 1993) describes an infrared glucose sensor mountable, for instance, on a wrist or finger. U.S. Pat. No. 5,433,197 (issued to Stark on Jul. 18, 1995) describes determination of blood glucose through illuminating a patient's eye with near-infrared radiation. U.S. Pat. Nos. 5,115,133, 5,146,091 and 5,197,951 (issued to Knudson on May 19, 1992, Sep. 8, 1992 and Jan. 19, 1993, respectively) describe measuring blood glucose within blood vessels of a tympanic membrane in a human ear through light absorption measurements. The specifications of all of these patents are incorporated herein by reference.
The most common current approaches to determining blood glucose levels still appear to involve obtaining a sample of the person's blood and then measuring the level of glucose in the sample. These approaches will not be reviewed here except to say that obtaining the blood sample necessarily involves an invasive technique. Generally, the person's skin is broken or lanced to cause an external flow of blood which is collected in some fashion for the glucose level determination. This can be both inconvenient and distressful for a person and it is an object of the present invention to avoid the step of obtaining a blood sample directly, at least on a routine or daily basis.
It is known that skin tissue, when immersed in an aqueous glucose solution, equilibrates linearly with the concentration of external glucose ("Glucose Entry into the Human Epidermis. I. The Concentration of Glucose in the Human Epidermis", K. M. Halprin, A. Ohkawara and K. Adachi, J. Invest. Dermatol., 49(6): 559, 1967; "Glucose Entry into the Human Epidermis. II. The Penetration of Glucose into the Human Epidermis in vitro", K. M. Halprin and A. Ohkawara, J Invest Derm., 49(6): 561, 1967). It has also been shown that that skin glucose can vary in synchrony with blood level glucose during standardized tolerance testing in vivo ("The Cutaneous Glucose Tolerance Test I. A, Rate Constant Formula for Glucose Disappearance from the Skin", R. M. Fusaro, J. A. Johnson and J. V. Pilsum, J. Invest. Dermatol., 42: 359, 1964; "The Cutaneous Glucose Tolerance Test", R. M. Fusaro and J. A. Johnson, J. Invest. Dermatol., 44: 230, 1965). It is also known that glucose levels equilibrate between blood and interstitial fluids in contact with blood vessels ("A Microdialysis Method Allowing Characterization of Intercellular Water Space in Human", P. Lonnroth, P.-A. Jansson and U. Smith, The American Journal of Physiology, 253 (Endocrinol. Metab., 16): E228-E231, 1987; "Assessment of Subcutaneous Glucose Concentration; Validation of the Wick Technique as a Reference for Implanted Electrochemical Sensors in Normal and Diabetic Dogs," U. Fischer, R. Ertle, P. Abel, K. Rebrin, E. Brunstein, H. Hahn von Dorsche and E. J. Freyse, Diabetologia, 30: 940, 1987). Implantation of dialysis needles equipped with glucose sensors has shown that orally ingested glucose load is reflected by parallel changes in skin tissue glucose.